[EN] Dravet syndrome (DS) is a rare childhood disease consisting of a type of epilepsy characterized
by a variety of seizures resistant to drugs, frequently induced by fever. The disease begins at a
few months of age and ...[+]

[EN] Dravet syndrome (DS) is a rare childhood disease consisting of a type of epilepsy characterized
by a variety of seizures resistant to drugs, frequently induced by fever. The disease begins at a
few months of age and usually results in motor and cognitive disability. This disease is due to
dominant mutations in the human SCN1A gene that encodes a voltage-activated sodium channel
essential for neuronal excitability. There is a lot of variability in the phenotype of the disease,
that is, there is no consensus symptomatology described for all patients, nor for those with the
same mutation.
For this study, the Drosophila melanogaster parabss1 model has been used because para is the
gene homologous to the SCN1A gene in the fruit fly and bss1 is a characteristic mutation of D.
melanogaster. In order to try to understand this variability present in the disease, some genes
that are candidates for genetic modifiers of the gene para have been tested in this model.
Genetic modifiers are genes that are not directly involved in the disease, but alter or influence
the expression of the function of another gene, segregating independently of the main
mutation. These genes are related to processes of neurodevelopment or synaptic
communication, and they have their corresponding counterpart in D. melanogaster. The genetic
strategy used to alter its expression is based on the use of the UAS-GAL4 system to express an
interfering RNA. The methodology for the study of these genes is the execution of crisis trials,
survival trials and locomotion trials.
In the trials, the connection of these modifying genes with the mutated parabss1 gene in the
disease phenotype has been verified. In the silencing of CG8916, Caα1T, KCNQ, nAChRα4, Clc-a
and Slo genes, important differences have been observed in the three tests performed:
decreased recovery time after a crisis, increased survival and increase in the length traveled
during an exploration time, thus revealing the silencing of these genes as a suppressor of the SD
phenotype. Toy is the only modifier gene in which its silencing is an enhancer of the SD
phenotype, showing a large decrease in the half-life of flies. These genes could act as therapeutic
targets and diagnostic tools for DS.[-]